Pancreatic CancerPhase 1ABC-101NCT01488513
ABC294640 in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing sphingosine kinase-2 inhibitor ABC294640 in people with Pancreatic Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by RedHill Biopharma Limited at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of ABC294640 in treating patients with advanced solid tumors. ABC294640 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Please note that the FDA OOPD is participating as a funding source. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- sphingosine kinase-2 inhibitor ABC294640
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Jul 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PART I:
- Patients with histologically confirmed solid organ carcinomas
- Tumor progression after receiving standard/approved chemotherapy or as first-line therapy for malignancies where there is no standard therapy
- One or more tumors measurable on computed tomography (CT) scan per RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of at least 3 months
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- Age > 18 years
- Signed, written Institutional Review Board (IRB)-approved informed consent
- A negative pregnancy test (if female)
- Acceptable liver function:
- Bilirubin =< 3 times upper limit of normal (ULN) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 2 baseline)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 3 x ULN (CTCAE Grade 1 baseline)
- Serum creatinine =< 1.5 X ULN (CTCAE Grade 1 baseline)
- Absolute neutrophil count >= 1000 cells/mm^3
- Acceptable hematologic status:
- Absolute neutrophil coun > 1000 cells/mm3
- Platelet count >= 75,000 (plt/mm^3) (CTCAE Grade 1 baseline)
- Hemoglobin >= 9 g/dL
- Acceptable blood sugar control:
- Fasting glucose value < 160 mg/dL (CTCAE Grade 1 baseline)
- Urinalysis: No clinically significant abnormalities
- Prothrombin time (PT) and partial thromboplastin time (PTT) =< 1.5 X ULN after correction of nutritional deficiencies that may contribute to prolonged PT/PTT
- For men and women of child-producing potential, willingness to use of effective contraceptive methods during the study; if female (or female partner of male subject), is either not of childbearing potential (defined as postmenopausal for >= 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing 1 of the following medically acceptable methods of birth control and agrees to continue with the regimen throughout the duration of the study:
- Oral, implantable or injectable contraceptives for 3 consecutive months before the baseline/randomization visit
- Total abstinence from sexual intercourse (>= 1 complete menstrual cycle before the baseline/randomization visit)
- Intrauterine device (IUD)
- Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream)
- PART II:
- To be eligible for inclusion in Part II, patients must meet the eligibility for Part 1 as well as the following:
- Patients with histologically confirmed HCC for whom there is no standard/approved chemotherapy
Who cannot join
- New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Pregnant or nursing women; NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within one month prior to study entry
- Unwillingness or inability to comply with procedures required in this protocol
- Known infection with human immunodeficiency virus (HIV)
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- Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
- Patients who are currently receiving any other investigational agent
- Patients who are receiving drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that cannot be stopped at least 7 days or 5 half-lives (whichever is longer) before starting treatment with ABC294640 and either replaced with another appropriate medication or not given for the duration of the clinical study
- Patients who are currently taking Coumadin or Coumadin derivatives
- Patients who have received any antineoplastic therapy within 1 month of starting treatment with ABC294640 or who have not adequately recovered from side effects and toxicities of previous antineoplastic therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
Official title: A Phase I, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of ABC294640 in Patients With Advanced Solid Tumors
This phase I trial studies the side effects and best dose of ABC294640 in treating patients with advanced solid tumors. ABC294640 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Please note that the FDA OOPD is participating as a funding source.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess safety and determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of ABC294640 (sphingosine kinase-2 inhibitor ABC294640) in patients with solid organ tumors. (Part I) II. To assess the safety and tolerability of ABC294640 at the MTD in an expanded cohort of hepatocellular carcinoma (HCC) patients. (Part II)
SECONDARY OBJECTIVES:
- To establish the dose of ABC294640 recommended for future phase II protocols. (Part I) II. To describe the pharmacokinetics of ABC294640 in patients with solid organ tumors. (Part I) III. To describe the effects of ABC294640 on plasma levels of sphingosine 1-phosphate in patients with solid organ tumors. (Part I) IV. To assess antitumor activity of ABC294640 in patients with solid organ tumors by objective radiographic assessment using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. (Part I) V. To describe the pharmacokinetics of ABC294640 in HCC patients. (Part II) VI. To describe the effects of ABC294640 on plasma levels of sphingosine 1-phosphate in HCC patients. (Part II) VII. To assess antitumor activity of ABC294640 in HCC patients by objective radiographic assessment using RECIST 1.1 criteria. (Part II)
OUTLINE: This is a dose-escalation study.
Patients receive sphingosine kinase-2 inhibitor ABC294640 orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up monthly for 1 year.
- Being tested
- sphingosine kinase-2 inhibitor ABC294640
- Keywords
- ABC294640, RedHill Biopharma, Ltd., ABC-101, Medical University of South Carolina, Apogee Biotechnology Corporation
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sphingosine kinase-2 inhibitor ABC294640Drug
Also called SK2 inhibitor ABC294640
Given PO Starting dose of ABC294640 250 mg once on day on Days 1-28 of each 28-day cycle. Subsequent cohort doses (if reached) are as follows: 250 BID, 500 BID, 750 BID, 1,000 BID, 1,500 BID, 2,000 BID, 2,500 BID
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Patients receive sphingosine kinase-2 inhibitor ABC294640 PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: sphingosine kinase-2 inhibitor ABC294640 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) defined as highest dose of ABC294640 at which 0 or 1 patient of 6 experiences a DLT.
MTD defined as the highest dose at which 0 or 1 patient of 6 experiences a DLT. The DLT rate will be estimated with its 95% confidence interval.
Measured: Patients will be followed until the point in time when no more than 1 of 6 patients has a Dose Limiting Toxicity (DLT) in cycle 1, and expected 54 days.
Safety assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0.
Assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0. Adverse events (AEs) will be coded by body system and summary tables with incidence rates of adverse events will be generated. Descriptive statistics of AEs will be reported by doses and for subsets of patients with serious adverse events (SAEs), patients who discontinue due to AEs, and patients with related AEs.
Measured: Weekly during course 1, bi-weekly for all subsequent courses, and at the end of treatment study-- expected to occur at an average of 6 months from study start.
Secondary outcomes (3)
Pharmacodynamic parameters for sphingosine kinase-2 inhibitor ABC294640
Area under the drug concentration over time curve (AUC), maximum concentration, minimum concentration, and time to maximum concentration will be calculated for each subject.
Measured: Days 1 and 28 of cycle 1 collected at prior to dose, 1, 2, 4, 8, 12, 24 hours post drug administration.
Pharmacodynamic parameters for sphingosine kinase-2 inhibitor ABC294640
Pharmacodynamic parameters for ABC294640 action will include measurement of plasma levels of S1P, including absolute concentration at each sampling time and chance from baseline concentration at each sampling time after drug administration.
Measured: Weekly during course 1, bi-weekly for all subsequent courses, and at the end of treatment study-- expected to occur at an average of 6 months from study start.
Tumor response rate
All patients who have measureable disease according to RECIST 1.1, received at least one cycle of treatment, and have had disease re-evaluated will be included.
Measured: Every 8 weeks till end of treatment study-- expected to occur at an average of 6 months from study start.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2011 (estimated)
- Study startAug 2011
- Primary completionAug 2014
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- RedHill Biopharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Apogee Biotechnology Corporation, Medical University of South Carolina, FDA Office of Orphan Products Development, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Carolyn Britten, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01488513
- Sponsor's protocol ID
- CTO 101504
- Other IDs
- NCI -2011-02993, G04102-00, R01FD004102-01
- Acronym
- ABC-101
- Status last verified
- Aug 2015
- First submitted
- 29 Sep 2011
- Last updated
- 7 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of ABC294640 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01488513
- Acronym / sponsor ID
- ABC-101 / CTO 101504
- Keywords
- ABC294640, RedHill Biopharma, Ltd., ABC-101, Medical University of South Carolina, Apogee Biotechnology Corporation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- RedHill Biopharma LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Apogee Biotechnology Corporation, Medical University of South Carolina, FDA Office of Orphan Products Development, National Cancer Institute (NCI)
- Study start
- Aug 2011
- Primary completion
- Aug 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 8 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of ABC294640 in treating patients with advanced solid tumors. ABC294640 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Please note that the FDA OOPD is participating as a funding source.
Detailed description
PRIMARY OBJECTIVES:
- To assess safety and determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of ABC294640 (sphingosine kinase-2 inhibitor ABC294640) in patients with solid organ tumors. (Part I) II. To assess the safety and tolerability of ABC294640 at the MTD in an expanded cohort of hepatocellular carcinoma (HCC) patients. (Part II)
SECONDARY OBJECTIVES:
- To establish the dose of ABC294640 recommended for future phase II protocols. (Part I) II. To describe the pharmacokinetics of ABC294640 in patients with solid organ tumors. (Part I) III. To describe the effects of ABC294640 on plasma levels of sphingosine 1-phosphate in patients with solid organ tumors. (Part I) IV. To assess antitumor activity of ABC294640 in patients with solid organ tumors by objective radiographic assessment using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. (Part I) V. To describe the pharmacokinetics of ABC294640 in HCC patients. (Part II) VI. To describe the effects of ABC294640 on plasma levels of sphingosine 1-phosphate in HCC patients. (Part II) VII. To assess antitumor activity of ABC294640 in HCC patients by objective radiographic assessment using RECIST 1.1 criteria. (Part II)
OUTLINE: This is a dose-escalation study.
Patients receive sphingosine kinase-2 inhibitor ABC294640 orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up monthly for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Drug: sphingosine kinase-2 inhibitor ABC294640Patients receive sphingosine kinase-2 inhibitor ABC294640 PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- PART I:
- Patients with histologically confirmed solid organ carcinomas
- Tumor progression after receiving standard/approved chemotherapy or as first-line therapy for malignancies where there is no standard therapy
- One or more tumors measurable on computed tomography (CT) scan per RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Key exclusion criteria (11 listed)
- New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Pregnant or nursing women; NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within one month prior to study entry
- Unwillingness or inability to comply with procedures required in this protocol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sphingosine kinase-2 inhibitor ABC294640Also: SK2 inhibitor ABC294640Given PO Starting dose of ABC294640 250 mg once on day on Days 1-28 of each 28-day cycle. Subsequent cohort doses (if reached) are as follows: 250 BID, 500 BID, 750 BID, 1,000 BID, 1,500 BID, 2,000 BID, 2,500 BID | Drug | Treatment (enzyme inhibitor therapy) |
Primary outcome
Maximum tolerated dose (MTD) defined as highest dose of ABC294640 at which 0 or 1 patient of 6 experiences a DLT.
Time frame: Patients will be followed until the point in time when no more than 1 of 6 patients has a Dose Limiting Toxicity (DLT) in cycle 1, and expected 54 days.
MTD defined as the highest dose at which 0 or 1 patient of 6 experiences a DLT. The DLT rate will be estimated with its 95% confidence interval.
Safety assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0.
Time frame: Weekly during course 1, bi-weekly for all subsequent courses, and at the end of treatment study-- expected to occur at an average of 6 months from study start.
Assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0. Adverse events (AEs) will be coded by body system and summary tables with incidence rates of adverse events will be generated. Descriptive statistics of AEs will be reported by doses and for subsets of patients with serious adverse events (SAEs), patients who discontinue due to AEs, and patients with related AEs.
3 secondary outcomes
Pharmacodynamic parameters for sphingosine kinase-2 inhibitor ABC294640
Time frame: Days 1 and 28 of cycle 1 collected at prior to dose, 1, 2, 4, 8, 12, 24 hours post drug administration.
Pharmacodynamic parameters for sphingosine kinase-2 inhibitor ABC294640
Time frame: Weekly during course 1, bi-weekly for all subsequent courses, and at the end of treatment study-- expected to occur at an average of 6 months from study start.
Tumor response rate
Time frame: Every 8 weeks till end of treatment study-- expected to occur at an average of 6 months from study start.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carolyn Britten, MD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sphingosine kinase-2 inhibitor ABC294640 in people with Pancreatic Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by RedHill Biopharma Limited at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) defined as highest dose of ABC294640 at which 0 or 1 patient of 6 experiences a DLT. (time frame: Patients will be followed until the point in time when no more than 1 of 6 patients has a Dose Limiting Toxicity (DLT) in cycle 1, and expected 54 days.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2020.